(A) Schematic of the FST design. (B–D) Male mice were administered VEH or KETSN (4 mg/kg, IP) 10 min prior to administration of 5-MeO (10 mg/kg, IP). Ketanserin completely blocked the HTR induced by 5-MeO (B), but did not block 5-MeO-induced hypolocomotion (C and D). (E) A pretest demonstrated that immobility in the FST was the same for all groups prior to compound administration. (F) Pretreatment with KETSN (4 mg/kg, IP) blocks the antidepressant-like effect of 5-MeO-DMT (10 mg/kg, IP) in the FST. 5-MeO = 5-methoxy-N,N-dimethyltryptamine; VEH = vehicle, KETSN = ketanserin. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, as compared to VEH – KETSN controls, one-way ANOVA with Dunnett’s post hoc test.